guest ::
| Home > Publications database > IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening. > print |
| Home > Publications database > IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening. > print |
| 001 | 298340 | ||
| 005 | 20250525020714.0 | ||
| 024 | 7 | _ | |a 10.1182/blood.2024027171 |2 doi |
| 024 | 7 | _ | |a pmid:39869826 |2 pmid |
| 024 | 7 | _ | |a 0006-4971 |2 ISSN |
| 024 | 7 | _ | |a 1528-0020 |2 ISSN |
| 024 | 7 | _ | |a altmetric:173892410 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2025-00244 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Pohly, Marcel F |0 0000-0003-0393-5840 |b 0 |
| 245 | _ | _ | |a IAP dependency of T-cell prolymphocytic leukemia identified by high-throughput drug screening. |
| 260 | _ | _ | |a Washington, DC |c 2025 |b American Society of Hematology |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1747725917_3491 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a 2025 May 15;145(20):2336-2352 |
| 520 | _ | _ | |a T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoid malignancy with limited treatment options. To discover new treatment targets for T-PLL, we performed high-throughput drug sensitivity screening on 30 primary patient samples ex-vivo. After screening over 2'800 unique compounds, we found T-PLL to be more resistant to most drug classes, including chemotherapeutics, compared to other blood cancers. Furthermore, we discovered previously not reported vulnerabilities of T-PLL. T-PLL cells exhibited a particular sensitivity to drugs targeting autophagy (thapsigargin, bafilomycin A1), nuclear export (selinexor), and inhibitor of apoptosis proteins (IAPs) (birinapant), sensitivities that were also shared by other T-cell malignancies. Through bulk and single-cell RNA-Sequencing we found these compounds to activate the toll-like-receptor (TLR) (bafilomycin A1), p53 (selinexor), and TNF-ɑ/NFκB signaling pathways (birinapant) in T-PLL cells. Focussing on birinapant for its potential in drug repurposing, we uncovered that IAP inhibitor-induced cell death was primarily necroptotic and dependent on TNF-ɑ. Through spectral flow cytometry we confirmed the absence of cleaved caspase-3 in IAP inhibitor treated T-PLL cells and show that IAP inhibition reduces the proliferation of T-PLL cells stimulated ex-vivo, while showing only a limited effect on non-malignant T-cells. In summary, our study maps the drug sensitivity of T-PLL across a broad range of targets and identifies new therapeutic approaches for T-PLL by targeting IAPs, XPO1 and autophagy, highlighting potential candidates for drug repurposing and novel treatment strategies. |
| 536 | _ | _ | |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312) |0 G:(DE-HGF)POF4-312 |c POF4-312 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 700 | 1 | _ | |a Putzker, Kerstin |0 P:(DE-He78)04eb74f47fce0fa7e60ef3880ee01ada |b 1 |u dkfz |
| 700 | 1 | _ | |a Scheinost, Sebastian |b 2 |
| 700 | 1 | _ | |a Ben Taarit, Lena |b 3 |
| 700 | 1 | _ | |a Walther, Tatjana |0 P:(DE-He78)e8feda17d03b95bda3e8717e79dc07b8 |b 4 |u dkfz |
| 700 | 1 | _ | |a Kummer, Sandra |b 5 |
| 700 | 1 | _ | |a Wertheimer, Tobias |0 0000-0002-8480-7391 |b 6 |
| 700 | 1 | _ | |a Lin, Minqi |b 7 |
| 700 | 1 | _ | |a Do, Thi Huong Lan |0 0000-0001-8058-4410 |b 8 |
| 700 | 1 | _ | |a Handler, Kristina |0 0000-0001-8952-6487 |b 9 |
| 700 | 1 | _ | |a Michler, Jan |b 10 |
| 700 | 1 | _ | |a Kivioja, Jarno |0 0000-0002-4046-0963 |b 11 |
| 700 | 1 | _ | |a Bach, Karsten |0 0000-0003-3622-1115 |b 12 |
| 700 | 1 | _ | |a Kisele, Samanta |0 0000-0003-0369-7854 |b 13 |
| 700 | 1 | _ | |a Kim, James |b 14 |
| 700 | 1 | _ | |a Dietrich, Sascha |b 15 |
| 700 | 1 | _ | |a Bornhauser, Beat |0 0000-0003-2890-3191 |b 16 |
| 700 | 1 | _ | |a Wong, Wendy Wei-Lynn |0 0000-0003-3155-1211 |b 17 |
| 700 | 1 | _ | |a Becher, Burkhard |0 0000-0002-1541-7867 |b 18 |
| 700 | 1 | _ | |a Moor, Andreas |0 0000-0001-8715-8449 |b 19 |
| 700 | 1 | _ | |a Lewis, Joe David |0 0000-0002-9926-1328 |b 20 |
| 700 | 1 | _ | |a Ficht, Xenia Maria |0 0000-0002-4534-8225 |b 21 |
| 700 | 1 | _ | |a Lu, Junyan |b 22 |
| 700 | 1 | _ | |a Huber, Wolfgang |b 23 |
| 700 | 1 | _ | |a Zenz, Thorsten |b 24 |
| 773 | _ | _ | |a 10.1182/blood.2024027171 |g p. blood.2024027171 |0 PERI:(DE-600)1468538-3 |n 20 |p 2336-2352 |t Blood |v 145 |y 2025 |x 0006-4971 |
| 909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:298340 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 1 |6 P:(DE-He78)04eb74f47fce0fa7e60ef3880ee01ada |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 4 |6 P:(DE-He78)e8feda17d03b95bda3e8717e79dc07b8 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF4-310 |0 G:(DE-HGF)POF4-312 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Funktionelle und strukturelle Genomforschung |x 0 |
| 914 | 1 | _ | |y 2025 |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b BLOOD : 2022 |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |d 2024-12-30 |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1190 |2 StatID |b Biological Abstracts |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1110 |2 StatID |b Current Contents - Clinical Medicine |d 2024-12-30 |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2024-12-30 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2024-12-30 |
| 915 | _ | _ | |a IF >= 20 |0 StatID:(DE-HGF)9920 |2 StatID |b BLOOD : 2022 |d 2024-12-30 |
| 920 | 1 | _ | |0 I:(DE-He78)W040-20160331 |k W040 |l Chemische Biologie Core Facility |x 0 |
| 920 | 1 | _ | |0 I:(DE-He78)B340-20160331 |k B340 |l Translationale Medizinische Onkologie |x 1 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-He78)W040-20160331 |
| 980 | _ | _ | |a I:(DE-He78)B340-20160331 |
| 980 | _ | _ | |a UNRESTRICTED |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|